The present invention is related to compositions and methods of treating microbial infections. Since antibiotics and other antimicrobial drugs first became widely used in the World War II era, they have saved countless lives and blunted serious complications of many feared diseases and infections. Over time, some bacteria have developed ways to circumvent the effects of antibiotics. Widespread use of antibiotics is thought to have spurred evolutionarily adaptations that enable bacteria to survive these powerful drugs. Other microbes such as viruses, fungi and parasites have developed resistance as well. Antimicrobial resistance provides a survival benefit to microbes and makes it harder to eliminate infections from the body. Ultimately, the increasing difficulty in fighting off microbes leads to an increased risk of acquiring infections in a hospital or other setting.
Further, bacteria and fungi form biofilms under certain conditions. When a group of bacteria or fungi accumulate on a surface and reach a particular cell density, they begin to secrete a polymeric substance that consists of polysaccharides, proteins and DNA and form a matrix in which the bacterial or fungal cells are entrenched. The multi-cellular aggregates or biofilms allow for individual bacterial or fungal cells or colonies of bacterial or fungal cells to exhibit coordinated behavior and confer upon the microorganism advantages including, for example, resistance to antibiotics and host immune systems. More specifically, biofilms are structured to allow respiration and fluid and nutrient exchange while preventing access of host immune cells such as phagocytes and preventing inhibitory or lytic concentrations of antimicrobials from reaching the microorganisms. As a result of these properties, infections that result from biofilm formation are notoriously difficult to eradicate and require the use of high concentrations of antimicrobial agents, removal of tissue, debridement of affected tissues and combination of these treatments. Therefore, there is a need to develop better compositions to treat microbial infections.
Mildly infected diabetic foot ulcer patients are currently treated with traditional wound care products because (1) no topical treatment is approved today for use in this population, (2) because clinicians refrain from using the many different available topical antibiotics because they are reported to be not completely effective and, (3) because clinicians refrain from using the more powerful systemic antibiotics (oral and IV antibiotics) at this stage of infection. While some of these patients respond to standard wound care (dressing changes and cleansing of the area), many progress rapidly to moderate to severe infections that require systemic antibiotics, and in some cases, hospitalization and limb amputation. Therefore, there is a need to develop methods and compositions to treat foot ulcers in diabetic patients.